Affinage

SERPINB3

Serpin B3 · UniProt P29508

Length
390 aa
Mass
44.6 kDa
Annotated
2026-06-13
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINB3 is an inhibitory-type serpin that uses its reactive center loop (RCL) to inhibit cysteine and serine proteases — including cathepsin L, calpain, and chymotrypsin — and thereby acts as a broad cytoprotective and pro-tumorigenic effector across epithelial cancers and tissue injury (PMID:9817978, PMID:21383048). Many of its downstream activities are RCL-dependent: protease inhibition is required for its suppression of NK cell chemotaxis (PMID:11280721) and for protection against radiation-induced cathepsin L-mediated lysosomal cell death (lysoptosis), where genetic knockout sensitizes cells to necrotic death and only wild-type, not RCL-mutant, protein restores protection (PMID:35022555). This cathepsin L-buffering function sustains survival of glioblastoma cancer stem cells (PMID:36103817). By inhibiting calpain, SERPINB3 prevents cleavage of MYC into its non-oncogenic form and additionally raises MYC via Yap/Hippo activation, stabilizing MYC to drive metabolic reprogramming and aggressive squamous/basal tumor phenotypes (PMID:26634820, PMID:37980563). SERPINB3 also drives epithelial-mesenchymal transition and pro-fibrogenic signaling through autocrine and paracrine routes — including TGF-β1 induction and activation of hepatic stellate cells — with EMT being independent of anti-protease activity but TGF-β1 induction requiring an intact RCL (PMID:20527027, PMID:20212457, PMID:28611447). It promotes tumor-permissive inflammation and immune evasion by inducing a prolonged non-lethal unfolded protein response that activates NF-κB and IL-6 (PMID:24759783, PMID:25213322), and by driving STAT-dependent CXCL1/CXCL8 and S100A8/S100A9 production that recruits myeloid-derived suppressor cells and suppresses cytotoxic T cells (PMID:37279067). SERPINB3 localizes to mitochondria where it inhibits respiratory Complex I to limit ROS and block permeability transition pore opening, contributing to apoptosis resistance and chemoresistance (PMID:24810714). Its expression is induced by oncogenic Ras via MAPK/PEA3 (PMID:24759783) and by hypoxia through HIF-2α in a redox-dependent manner (PMID:25544768), and is repressed post-transcriptionally by miR-122 (PMID:30717317).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Established the biochemical identity of SERPINB3 as a functional protease inhibitor rather than a non-inhibitory serpin, defining its core molecular activity.

    Evidence In vitro protease inhibition assays with recombinant protein against chymotrypsin and cathepsin L

    PMID:9817978

    Open questions at the time
    • Full physiological substrate spectrum not defined in this assay
    • No cellular or in vivo context for the inhibition
  2. 2001 High

    Linked SERPINB3 protease activity to immune evasion by showing it suppresses NK cell chemotaxis in an RCL-dependent manner, and that knockdown restores apoptosis and NK infiltration in tumors.

    Evidence NK cell migration assay with RCL mutant; antisense knockdown in nude mouse SCC tumors with IHC

    PMID:11280721

    Open questions at the time
    • Protease target mediating antichemotactic effect not identified
    • Mechanism connecting protease inhibition to migration suppression unresolved
  3. 2010 High

    Showed SERPINB3 drives EMT and pro-fibrogenic TGF-β1 signaling, separating an anti-protease-independent EMT/scatter activity from an RCL-dependent TGF-β1 induction.

    Evidence Transfection, exogenous recombinant protein, active-loop-deleted mutants, invasion/ultrastructure assays in HepG2/Huh7/hepatocytes

    PMID:20212457 PMID:20527027

    Open questions at the time
    • Receptor or signaling intermediary for paracrine scatter activity unknown
    • How an RCL-independent activity operates mechanistically is unresolved
  4. 2011 High

    Provided structural basis for SERPINB3 inhibition and showed an RCL polymorphism (Gly351Ala) tunes cathepsin L/papain and JNK1 inhibitory potency.

    Evidence X-ray crystallography at 2.7 Å, in vitro kinetics with recombinant variants, JNK activity assay, homology modelling

    PMID:21383048

    Open questions at the time
    • Functional consequence of the polymorphism in vivo not established
    • Mechanism of JNK inhibition not biochemically defined
  5. 2014 High

    Defined SERPINB3 as an oncogenic effector downstream of Ras/MAPK/PEA3 that sustains tumor inflammation by inducing a non-lethal UPR-driven NF-κB/IL-6 program, replicated in two independent epithelial systems.

    Evidence Reporter assays, reciprocal KD/OE, UPR/NF-κB pathway readouts, IL-6 ELISA, mouse tumor models

    PMID:24759783 PMID:25213322

    Open questions at the time
    • How protease inhibition triggers the UPR is unclear
    • Molecular link between SERPINB3 and proteostasis disruption undefined
  6. 2014 High

    Identified a mitochondrial localization and function for SERPINB3, where it inhibits Complex I to limit ROS and block PTP opening, providing a mechanism for chemoresistance and reduced cytochrome c release.

    Evidence Subcellular fractionation, mitochondrial ROS and PTP assays, co-IP with Complex I, viability assays with pro-oxidant drugs

    PMID:19332150 PMID:24810714 PMID:25332258

    Open questions at the time
    • How a serpin reaches the mitochondrial inner compartment is unknown
    • Direct Complex I subunit target not mapped
  7. 2015 High

    Established calpain inhibition as a route by which SERPINB3 stabilizes MYC, complemented by Yap/Hippo-mediated transcriptional MYC upregulation.

    Evidence In vitro calpain inhibition assay, hepatoma transfection, transgenic mice, Yap pathway analysis, co-IP

    PMID:26634820

    Open questions at the time
    • Mechanism linking SERPINB3 to Yap activation not resolved
    • Relative contribution of the two MYC mechanisms unquantified
  8. 2015 High

    Placed SERPINB3 in hypoxic signaling, showing HIF-2α (not HIF-1α) drives its transcription and extracellular release in a ROS-dependent manner.

    Evidence ChIP, HIF-1α/HIF-2α siRNA, ROS measurement, qRT-PCR/Western under hypoxia

    PMID:25544768

    Open questions at the time
    • Source of the redox signal selecting HIF-2α not defined
    • Function of secreted SERPINB3 in the hypoxic niche unclear
  9. 2017 High

    Confirmed paracrine pro-fibrogenic activity, showing recombinant SERPINB3 activates hepatic stellate cells and hepatocyte-overexpressing mice develop more fibrosis under chronic injury.

    Evidence Recombinant protein on HSC/MF and LX2 cells; CCl4 and MCD-diet transgenic mouse models; qRT-PCR/IHC

    PMID:28611447

    Open questions at the time
    • Stellate-cell receptor for SERPINB3 not identified
    • Signaling pathway driving migration vs. proliferation split unresolved
  10. 2019 High

    Identified post-transcriptional control of SERPINB3 by miR-122 and linked its expression to sorafenib resistance.

    Evidence Luciferase 3'UTR reporter, miR-122 transfection/inhibition, Western blot, viability assay

    PMID:30717317

    Open questions at the time
    • Physiological contexts where miR-122 regulates SERPINB3 not mapped
    • Mechanism of SERPINB3-driven drug resistance not specified here
  11. 2022 High

    Demonstrated that RCL-dependent cathepsin L inhibition protects against radiation-induced lysoptosis and sustains cancer stem cell survival, cementing the protease-inhibition-to-cell-death-protection axis.

    Evidence CRISPR KO with WT vs. RCL-mutant rescue, cathepsin L genetic KD, cell death assays, transcriptomics; CSC shRNA depletion with xenografts and radiosensitivity assays

    PMID:35022555 PMID:36103817

    Open questions at the time
    • Trigger releasing cathepsin L to the cytosol not defined
    • Generality across non-irradiated lysosomal death stimuli unclear
  12. 2022 High

    Established SERPINB3 as a driver of immune evasion via STAT-dependent chemokine and alarmin production that recruits MDSCs and suppresses cytotoxic T cells.

    Evidence OE/KD, ruxolitinib and STAT siRNA, monocyte/MDSC migration, mouse tumor models, immune-infiltrate flow cytometry

    PMID:37279067

    Open questions at the time
    • How SERPINB3 activates STAT signaling is not defined
    • Direct vs. indirect role of protease inhibition in this axis unresolved
  13. 2022 High

    Showed the SERPINB3 scaffold is RCL-programmable, generating engineered variants that inhibit furin/TMPRSS2 and block SARS-CoV-2 entry, confirming RCL identity dictates target specificity.

    Evidence RCL mutagenesis, kinetic inhibition assays, pseudoparticle entry and live-virus replication assays

    PMID:36293378

    Open questions at the time
    • Native SERPINB3 does not target these proteases
    • In vivo antiviral utility not tested
  14. 2022 Medium

    Connected SERPINB3 to DNA crosslink repair, showing its HPV-driven downregulation impairs USP1-dependent FANCD2-FANCI deubiquitination and sensitizes HNSCC to cisplatin.

    Evidence siRNA KD, FANCD2-FANCI ubiquitination assays, DNA repair assays, PDX with nanoparticle siRNA

    PMID:36382555

    Open questions at the time
    • Mechanistic link between a protease inhibitor and USP1 activity unexplained
    • Single-lab finding without reciprocal validation
  15. 2014 High

    Extended SERPINB3 biology beyond cancer, showing the mouse homolog promotes epidermal barrier dysfunction and S100A8-driven inflammation in atopic dermatitis.

    Evidence Serpinb3a-null mice with allergen challenge, TEWL, RNA-seq; human keratinocyte siRNA

    PMID:25111616

    Open questions at the time
    • Protease target in skin inflammation not identified
    • Relationship between human SERPINB3 and mouse Serpinb3a function not fully reconciled
  16. 2025 Medium

    Placed SERPINB3 downstream of a TMEM65-OXPHOS-ROS-HIF1α axis in triple-negative breast cancer, driving stemness and cisplatin resistance.

    Evidence TMEM65 KD/OE, ROS measurement, HIF1α inhibition, SERPINB3 expression analysis, cisplatin assays, in vivo models

    PMID:40546127

    Open questions at the time
    • SERPINB3 not directly manipulated as primary subject
    • Apparent HIF1α dependence contrasts with HIF-2α selectivity reported in liver cancer

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SERPINB3 transduces protease inhibition into the broad set of downstream programs (UPR/NF-κB, STAT signaling, Yap activation, mitochondrial Complex I inhibition) at the molecular level remains unresolved.
  • No unifying mechanism connecting cytosolic protease inhibition to nuclear/mitochondrial signaling outputs
  • Receptors mediating paracrine/extracellular SERPINB3 activity unidentified
  • How SERPINB3 localizes across cytosol, mitochondria, and cell surface is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140096 catalytic activity, acting on a protein 5
Localization
GO:0005576 extracellular region 2 GO:0005739 mitochondrion 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CAPNCTSLMYCNDUFS (COMPLEX I)

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Recombinant SERPINB3 (SCCA1) inhibits chymotrypsin and cathepsin L in vitro, establishing it as an inhibitory-type serpin targeting cysteine and serine proteases. In vitro protease inhibition assay with recombinant protein Tumour biology High 9817978
2001 SERPINB3 (SCCA1) suppresses NK cell migration induced by monocyte chemoattractant protein-1 in vitro, and this antichemotactic effect is abrogated by mutation of the reactive site loop, demonstrating that the anti-protease activity is required. NK cell migration assay with recombinant SCCA1 and reactive-site loop mutant Cancer research High 11280721
2001 Antisense suppression of SCCA (SERPINB3) in SCC tumor cells in vivo leads to increased apoptosis and NK cell infiltration, reducing tumor growth in nude mice. Antisense retroviral knockdown in vivo + immunohistochemistry of tumor tissue Cancer research Medium 11280721
2010 SERPINB3 expression in HepG2 cells induces epithelial-mesenchymal transition (EMT), evidenced by decreased E-cadherin, increased β-catenin and vimentin, loss of desmosomes, and increased cell migration, invasion, and anchorage-independent growth. These effects occur at both autocrine and paracrine levels and are independent of the anti-protease activity of the protein (active-loop deleted mutant retains scatter activity). Stable transfection of SERPINB3 in HepG2 cells; exogenous recombinant protein addition to HepG2/MDCK cells; active-loop deleted mutant; wound healing/invasion assays; ultrastructural analysis The Journal of pathology High 20527027
2010 SERPINB3 upregulates TGF-β1 mRNA and protein in transfected hepatocytes (primary human hepatocytes, HepG2, Huh7), and the integrity of the reactive site loop is required for this effect. Transfection of intact SERPINB3 or reactive-site loop deleted mutants; qRT-PCR and immunoassay for TGF-β1; correlation in liver biopsies Laboratory investigation High 20212457
2011 Crystal structure of wild-type SERPINB3 resolved at 2.7 Å, and molecular modelling revealed that the SCCA-PD polymorphic variant (Gly351Ala in reactive center loop) has increased hydrophobic profile, conferring greater cathepsin L and papain inhibitory activity and higher JNK1 inhibitory effect compared to wild-type. X-ray crystallography; in vitro kinetic analysis with recombinant proteins; JNK activity assay; 3D homology modelling Experimental biology and medicine High 21383048
2014 SERPINB3 is transcriptionally upregulated by oncogenic Ras via the MAPK pathway and the ETS family transcription factor PEA3. Increased SERPINB3 expression leads to inhibition of protein turnover, induction of the unfolded protein response (UPR), and NF-κB activation, which are essential for Ras-mediated cytokine production (e.g., IL-6) and tumor growth. Transcriptional reporter assays; genetic knockdown/overexpression; NF-κB and UPR pathway biochemical assays; mouse tumor models Nature communications High 24759783
2014 SERPINB3 (SCCA1) overexpression in mammary epithelial cells promotes oncogenic transformation and EMT, and induces a prolonged non-lethal UPR that activates NF-κB and IL-6 autocrine signaling to drive pro-tumorigenic inflammation. Stable overexpression and siRNA knockdown; UPR and NF-κB reporter assays; IL-6 ELISA; mouse mammary tumor model Cancer research High 25213322
2014 SERPINB3 localizes to mitochondrial inner compartments (fraction increases under oxidative stress) and protects hepatoma cells from doxorubicin/cisplatin-induced death by inhibiting mitochondrial respiratory Complex I, thereby reducing ROS generation and preventing mitochondrial permeability transition pore opening. Subcellular fractionation; mitochondrial ROS measurement; PTP opening assays; cell viability assays with pro-oxidant chemotherapeutics; co-immunoprecipitation with Complex I Oncotarget High 24810714
2015 SERPINB3 upregulates Myc through two mechanisms in hepatoma cells and transgenic mice: (1) direct inhibition of calpain protease activity, preventing calpain-mediated cleavage of Myc into its non-oncogenic cytoplasmic form (Myc-nick); (2) indirect activation of the Yap/Hippo pathway, which transcriptionally increases Myc. Recombinant SerpinB3 inhibits calpain activity in vitro. Transgenic mouse overexpression; hepatoma cell transfection; in vitro calpain inhibition assay; Yap pathway analysis; co-IP; Western blot Scientific reports High 26634820
2015 Hypoxia up-regulates SERPINB3 transcription, protein synthesis and extracellular release in liver cancer cells specifically through HIF-2α (not HIF-1α) binding to the SERPINB3 promoter, in a redox-sensitive manner requiring intracellular ROS generation. ChIP assay; siRNA silencing of HIF-1α and HIF-2α; ROS measurement; qRT-PCR and Western blot; hypoxia exposure experiments Oncotarget High 25544768
2017 Exogenous recombinant SerpinB3 added to activated hepatic stellate cells (HSC/MFs and LX2) upregulates pro-fibrogenic gene expression and promotes oriented migration but not proliferation. In transgenic mice overexpressing SerpinB3 in hepatocytes, chronic liver injury leads to increased fibrogenic gene expression, collagen deposition, and αSMA-positive HSC/MFs, confirming paracrine pro-fibrogenic activity. Recombinant protein addition to primary HSC/MF cultures and LX2 cells; transgenic mouse models (CCl4 and MCD diet); qRT-PCR; immunohistochemistry Scientific reports High 28611447
2019 MiR-122 directly targets the SERPINB3 mRNA 3'UTR as demonstrated by luciferase assay; miR-122 transfection decreased SERPINB3 mRNA and protein, while miR-122 inhibition increased SERPINB3 expression. Overexpression of SERPINB3 blunted the sensitizing effect of miR-122 on sorafenib treatment. Luciferase reporter assay; miR-122 transfection/inhibition; Western blot; cell viability assay Journal of clinical medicine High 30717317
2022 SERPINB3 inhibits cathepsin L and protects cervical cancer cells from radiation-induced lysoptosis (lysosomal cell death). Genetic knockout of SERPINB3 sensitizes cells to radiation-induced necrotic death; rescue with wild-type SERPINB3 but not a reactive site loop mutant restores protection, demonstrating that protease inhibitory activity is required. CRISPR/genetic knockout; wild-type vs. reactive-site loop mutant rescue; cell death assays (necrosis, apoptosis markers); cathepsin L genetic knockdown; transcriptomics Communications biology High 35022555
2022 SERPINB3 suppresses antitumor immunity by promoting STAT-dependent expression of chemokines CXCL1/CXCL8 and alarmins S100A8/S100A9, which recruit monocytes and myeloid-derived suppressor cells (MDSCs), thereby inhibiting cytotoxic T cell function. Inhibition of STAT activation by ruxolitinib or siRNA abrogates CXCL1/8 and S100A8/A9 expression in SERPINB3-expressing cells. SERPINB3 overexpression/knockdown; STAT inhibitor (ruxolitinib); STAT siRNA; monocyte/MDSC migration assays; mouse tumor models; flow cytometry of immune infiltrates The Journal of clinical investigation High 37279067
2022 SerpinB3 is essential for glioblastoma cancer stem cell (CSC) survival and maintenance by buffering cathepsin L-mediated lysosomal cell death; knockdown of SerpinB3 increases cathepsin L-dependent apoptosis and radiosensitivity in CSCs. Genetic depletion (shRNA/siRNA); cathepsin L activity/apoptosis assays; CSC sphere formation; mouse xenograft models; radiation sensitivity assays Cell reports High 36103817
2023 SERPINB3 inhibits the cysteine protease calpain, a key enzyme in the MYC degradation pathway, thereby stabilizing MYC and driving metabolic reprogramming (heightened carnitine/acylcarnitine and amino acid metabolism) and the basal-like/squamous subtype in pancreatic cancer. SERPINB3 transgene expression enhances invasion in vitro and promotes lung metastasis in a xenograft model. SERPINB3 transgene expression; in vitro invasion assays; mouse xenograft model; calpain activity assays; metabolome analyses Cell reports High 37980563
2022 SERPINB3 downregulation (by HPV-E6/E7) reduces USP1-mediated deubiquitination of FANCD2-FANCI in the Fanconi anemia DNA repair pathway, thereby impairing cisplatin-induced DNA interstrand crosslink repair and increasing HNSCC cell apoptosis. SERPINB3 siRNA knockdown; FANCD2-FANCI ubiquitination assays; DNA damage repair assays; patient-derived xenograft model with nanoparticle siRNA delivery Advanced science Medium 36382555
2014 SERPINB3 is expressed on the surface of CD27+ B lymphocytes in healthy individuals; this surface expression is reduced in HCV-infected patients and absent in SLE patients. Flow cytometry; confocal microscopy; correlation with CD27 expression Experimental biology and medicine Medium 22829702
2014 SERPINB3 is expressed in hepatic progenitor cells (EpCAM+ sorted cells from fetal and adult livers, CK-7/CK-19/EpCAM/CD-90 positive cells in cirrhotic livers); in a mouse model of liver injury, SerpinB3 expression progressively increases while activated caspase-3 decreases, consistent with an anti-apoptotic role in progenitor cells. Cell sorting; immunohistochemistry; RT-PCR with sequencing; mouse injury model (LPS/D-galactosamine) BMC cell biology Medium 24517394
2014 SERPINB3 attenuates cytochrome c release from mitochondria, contributing to apoptosis resistance. This was documented in vitro and in vivo across multiple studies. Cytochrome c release assay; transfection; in vitro apoptosis induction Autoimmunity reviews / Annals of hepatology (review citing in vitro and in vivo experiments) Medium 19332150 25332258
2014 In atopic dermatitis, SERPINB3/B4 (mouse homolog Serpinb3a) promotes barrier dysfunction and early inflammatory responses. Serpinb3a-null mice show attenuated transepidermal water loss, reduced epidermal thickness, and reduced skin inflammation after allergen exposure. Silencing of SERPINB3/B4 in human keratinocytes decreased S100A8 expression, placing SERPINB3/B4 upstream of the S100A8-mediated inflammatory response. Serpinb3a knockout mouse; topical allergen challenge; TEWL measurement; RNA-seq; siRNA silencing in human keratinocytes The Journal of investigative dermatology High 25111616
2020 TEAD4 transcriptionally regulates SERPINB3/B4 expression in psoriatic keratinocytes, and SERPINB3/B4 mediates TEAD4-dependent chemokine secretion that promotes T cell migration. TEAD4 siRNA knockdown; SERPINB3/B4 siRNA; chemokine ELISA; T cell migration assay Immunobiology Medium 32962824
2022 RCL-mutagenesis of SERPINB3 scaffold can redirect its inhibitory specificity: replacing the native RCL with sequences targeting furin or TMPRSS2 generates variants that inhibit these proteases (not cathepsin L), block SARS-CoV-2 spike protein cleavage in vitro, and suppress SARS-CoV-2 replication in cells. The TMPRSS2-targeting variant (B3-TMP) shows 18-fold improvement in inhibition rate constant over alpha-1 antitrypsin. Reactive center loop mutagenesis; in vitro protease inhibition kinetic assays; pseudoparticle entry assay; live virus replication assay International journal of molecular sciences High 36293378
2017 SERPINB3 induces a positive feedback loop between COX-2 and β-catenin in colorectal cancer cells; cell lines with high SerpinB3 expression show higher COX-2 and β-catenin levels, greater proliferation, and invasion compared to controls. Cell line comparison with differential SERPINB3 expression; Western blot for COX-2 and β-catenin; proliferation and invasion assays Oncotarget Medium 28178650
2025 SERPINB3 expression is transcriptionally activated by HIF1α downstream of ROS produced by TMEM65-enhanced OXPHOS in triple-negative breast cancer; SERPINB3 in turn promotes TNBC stemness, progression, and cisplatin resistance. TMEM65 knockdown/overexpression; ROS measurement; HIF1α inhibition; SERPINB3 expression analysis; cisplatin sensitivity assays; in vivo tumor models Advanced science Medium 40546127

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature. Nature communications 238 30202019
2011 Tumor-associated macrophages in the cutaneous SCC microenvironment are heterogeneously activated. The Journal of investigative dermatology 145 21307877
2004 Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells. Oncogene 105 14724590
1995 CEA, CYFRA21-1 and SCC in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 97 8581396
2009 SERPINB3, apoptosis and autoimmunity. Autoimmunity reviews 87 19332150
2016 SERPINB3 and B4: From biochemistry to biology. Seminars in cell & developmental biology 86 27637160
2006 Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression. Molecular therapy : the journal of the American Society of Gene Therapy 84 16455304
2014 SERPINB3/B4 contributes to early inflammation and barrier dysfunction in an experimental murine model of atopic dermatitis. The Journal of investigative dermatology 77 25111616
2015 Suppression of TGFβ and Angiogenesis by Type VII Collagen in Cutaneous SCC. Journal of the National Cancer Institute 76 26476432
2010 SERPINB3 induces epithelial-mesenchymal transition. The Journal of pathology 76 20527027
2001 Suppression of a squamous cell carcinoma (SCC)-related serpin, SCC antigen, inhibits tumor growth with increased intratumor infiltration of natural killer cells. Cancer research 74 11280721
2014 Oncogenic Ras induces inflammatory cytokine production by upregulating the squamous cell carcinoma antigens SerpinB3/B4. Nature communications 73 24759783
1989 Characterization of human laryngeal primary and metastatic squamous cell carcinoma cell lines UM-SCC-17A and UM-SCC-17B. Cancer research 68 2790823
2019 The role of squamous cell carcinoma antigen (SCC Ag) in outcome prediction after concurrent chemoradiotherapy and treatment decisions for patients with cervical cancer. Radiation oncology (London, England) 66 31416463
1998 SCC antigen in malignant and nonmalignant squamous lesions. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 63 9817981
2014 SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling. Cancer research 61 25213322
2007 Restriction endonuclease inhibitor IPI* of bacteriophage T4: a novel structure for a dedicated target. Journal of molecular biology 61 18037438
2014 SERPINB3 protects from oxidative damage by chemotherapeutics through inhibition of mitochondrial respiratory complex I. Oncotarget 54 24810714
2012 Risk stratification in oral cavity squamous cell carcinoma by preoperative CRP and SCC antigen levels. Annals of surgical oncology 50 22576068
2015 Hypoxia up-regulates SERPINB3 through HIF-2α in human liver cancer cells. Oncotarget 49 25544768
2003 Caenorhabditis elegans EVL-14/PDS-5 and SCC-3 are essential for sister chromatid cohesion in meiosis and mitosis. Molecular and cellular biology 48 14560015
1997 Diagnostic value of SCC, CEA and CYFRA 21.1 in lung cancer: a Bayesian analysis. The European respiratory journal 46 9072992
2010 SERPINB3 modulates TGF-beta expression in chronic liver disease. Laboratory investigation; a journal of technical methods and pathology 44 20212457
2003 CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 42 14639127
2019 MiR-122 Targets SerpinB3 and Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma. Journal of clinical medicine 41 30717317
1998 Biological role of SCC antigen. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 41 9817978
2020 Machine Learning Based Radiomic HPV Phenotyping of Oropharyngeal SCC: A Feasibility Study Using MRI. The Laryngoscope 38 33070337
2023 SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer. Cell reports 37 37980563
2011 Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the genesis of this tumour? European journal of cancer (Oxford, England : 1990) 35 21737255
1992 Expression of mRNA of SCC antigen in squamous cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 35 1290029
2015 SerpinB3 and Yap Interplay Increases Myc Oncogenic Activity. Scientific reports 31 26634820
2023 SCCA1/SERPINB3 suppresses antitumor immunity and blunts therapy-induced T cell responses via STAT-dependent chemokine production. The Journal of clinical investigation 30 37279067
2013 Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and apoptosis induction. PloS one 30 24098753
2000 Specific detection and quantitation of SCC antigen 1 and SCC antigen 2 mRNAs by fluorescence-based asymmetric semi-nested reverse transcription PCR. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 30 10867615
1998 Bacteriophage T4, a model system for understanding the mechanism of type II topoisomerase inhibitors. Biochimica et biophysica acta 30 9748648
2018 The genomic landscape of UM-SCC oral cavity squamous cell carcinoma cell lines. Oral oncology 29 30527230
2022 SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation. Communications biology 28 35022555
2015 Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). Journal of the American Academy of Dermatology 28 26138646
1999 Immunocytochemical detection of hMSH2 and hMLH1 expression in oral SCC. Anticancer research 27 10368636
2017 SerpinB3 Promotes Pro-fibrogenic Responses in Activated Hepatic Stellate Cells. Scientific reports 26 28611447
2021 The Tumor Microenvironment in SCC: Mechanisms and Therapeutic Opportunities. Frontiers in cell and developmental biology 25 33634137
2020 Epidemiology and Patient Distribution of Oral Cavity and Oropharyngeal SCC in Canada. Journal of cutaneous medicine and surgery 25 32238063
2016 Pso p27, a SERPINB3/B4-derived protein, is most likely a common autoantigen in chronic inflammatory diseases. Clinical immunology (Orlando, Fla.) 25 27871892
2012 SCC-S2 is overexpressed in colon cancers and regulates cell proliferation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 22886548
2012 E-cadherin in oral SCC: an analysis of the confusing literature and new insights related to its immunohistochemical expression. Histology and histopathology 24 22207548
2022 SerpinB3 drives cancer stem cell survival in glioblastoma. Cell reports 23 36103817
2021 The protease-inhibitor SerpinB3 as a critical modulator of the stem-like subset in human cholangiocarcinoma. Liver international : official journal of the International Association for the Study of the Liver 23 34478594
2019 Antitumor Effect of Albendazole on Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 23 31281836
2019 Pten loss in Lgr5+ hair follicle stem cells promotes SCC development. Theranostics 23 31754399
1998 Factors regulating SCC antigen expression in squamous cell carcinoma of the uterine cervix. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 9817979
2016 ALA-PDT inhibits proliferation and promotes apoptosis of SCC cells through STAT3 signal pathway. Photodiagnosis and photodynamic therapy 21 26805005
2014 Role of SERPINB3 in hepatocellular carcinoma. Annals of hepatology 21 25332258
2005 VEGF-subtype specific protection of SCC and HUVECs from radiation induced cell death. International journal of molecular medicine 21 15583841
2017 ERK1/2, JNK and STAT3 activation and correlation with tumor differentiation in oral SCC. Histology and histopathology 20 28090628
2014 Hepatic progenitor cells express SerpinB3. BMC cell biology 20 24517394
2014 The molecular signature of impaired diabetic wound healing identifies serpinB3 as a healing biomarker. Diabetologia 20 24962668
2004 SCC-112, a novel cell cycle-regulated molecule, exhibits reduced expression in human renal carcinomas. Gene 20 15019998
2017 SerpinB3 upregulates the Cyclooxygenase-2 / β-Catenin positive loop in colorectal cancer. Oncotarget 18 28178650
1991 Different behaviors in the production and release of SCC antigen in squamous-cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 18 1705047
2022 SerpinB3 as a Pro-Inflammatory Mediator in the Progression of Experimental Non-Alcoholic Fatty Liver Disease. Frontiers in immunology 17 35874657
2019 Tumor Suppressive Function of NQO1 in Cutaneous Squamous Cell Carcinoma (SCC) Cells. BioMed research international 17 31886179
2016 Management of BCC and SCC of the Head and Neck. Cancer control : journal of the Moffitt Cancer Center 17 27556662
2012 IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease. PloS one 17 22808225
2012 SERPINB3 expression on B-cell surface in autoimmune diseases and hepatitis C virus-related chronic liver infection. Experimental biology and medicine (Maywood, N.J.) 17 22829702
2011 Increased antiprotease activity of the SERPINB3 polymorphic variant SCCA-PD. Experimental biology and medicine (Maywood, N.J.) 17 21383048
2022 HPV Enhances HNSCC Chemosensitization by Inhibiting SERPINB3 Expression to Disrupt the Fanconi Anemia Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 16 36382555
2019 Immunotherapy and other systemic therapies for cutaneous SCC. Oral oncology 16 31715538
2021 Dynamics of somatic cell count (SCC) and differential SCC during and following intramammary infections. Journal of dairy science 15 33455778
2015 Frequency of squamous cell carcinoma (SCC) invasion in transected SCC in situ referred for Mohs surgery: the Dartmouth-Hitchcock experience. International journal of dermatology 15 25920731
2002 Beyond the ABCs of CKC and SCC. Do centromeres orchestrate sister chromatid cohesion or vice versa? European journal of biochemistry 15 11985612
2023 SERPINB3, Adult-Onset Immunodeficiency, and Generalized Pustular Psoriasis. Genes 14 36833193
2022 Reactive Centre Loop Mutagenesis of SerpinB3 to Target TMPRSS2 and Furin: Inhibition of SARS-CoV-2 Cell Entry and Replication. International journal of molecular sciences 14 36293378
2021 Impact of HSP90α, CEA, NSE, SCC, and CYFRA21-1 on Lung Cancer Patients. Journal of healthcare engineering 14 34721827
2020 UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines. Journal of cancer research and clinical oncology 14 32865618
2017 SLNB in cutaneous SCC: A review of the current state of literature and the direction for the future. Journal of surgical oncology 14 28672047
2014 MicroRNAs and SerpinB3 in hepatocellular carcinoma. Life sciences 14 24496037
2007 SCC-112 gene is involved in tumor progression and promotes the cell proliferation in G2/M phase. Journal of cancer research and clinical oncology 14 17846787
2020 TEAD4 transcriptional regulates SERPINB3/4 and affect crosstalk between keratinocytes and T cells in psoriasis. Immunobiology 13 32962824
2018 Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours. Anticancer research 13 29491058
2022 High p62 expression suppresses the NLRP1 inflammasome and increases stress resistance in cutaneous SCC cells. Cell death & disease 12 36581625
2017 Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review. The Laryngoscope 12 28411387
2015 Targeting mTOR and AREG with everolimus, sunitinib and sorafenib in HPV-positive and -negative SCC. Anticancer research 12 25862847
2015 Tumstatin induces apoptosis mediated by Fas signaling pathway in oral squamous cell carcinoma SCC-VII cells. Oncology letters 12 26622617
1998 Endonuclease II of coliphage T4: a recombinase disguised as a restriction endonuclease? Molecular microbiology 12 9515694
2024 BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations. Medicina (Kaunas, Lithuania) 11 38792976
2024 SerpinB3: A Multifaceted Player in Health and Disease-Review and Future Perspectives. Cancers 11 39061218
2021 SCC: an accurate imputation method for scRNA-seq dropouts based on a mixture model. BMC bioinformatics 11 33407064
2018 SerpinB3 induces dipeptidyl-peptidase IV/CD26 expression and its metabolic effects in hepatocellular carcinoma. Life sciences 11 29524519
2010 Expression of VEGF, VEGF-C and VEGFR-2 in in situ and invasive SCC of cervix. Frontiers in bioscience (Elite edition) 11 20036889
2025 MYC/TET3-Regulated TMEM65 Activates OXPHOS-SERPINB3 Pathway to Promote Progression and Cisplatin Resistance in Triple-Negative Breast Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 10 40546127
2021 Low P66shc with High SerpinB3 Levels Favors Necroptosis and Better Survival in Hepatocellular Carcinoma. Biology 10 33922660
2016 Novel SCC mutation in a patient of Mexican descent with sex reversal, salt-losing crisis and adrenal failure. Endocrinology, diabetes & metabolism case reports 10 27855232
2015 Serum and Saliva MMP-3 in Patients with OLP and Oral SCC. The journal of contemporary dental practice 10 25906800
2014 Adaptive evolution and divergence of SERPINB3: a young duplicate in great Apes. PloS one 10 25133778
2011 Tissue specific expression and estrogen regulation of SERPINB3 in the chicken oviduct. General and comparative endocrinology 10 22026959
2008 Squamous cell carcinoma antigen-1 (SERPINB3) polymorphism in chronic liver disease. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 10 18657489
2001 Expression of SCC in ovarian granulosa cells and cultured cells, induced rapid structural changes in mitochondria. Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 10 11729997
1990 Functional expression of microsomal and mitochondrial cytochrome P-450 (d and SCC) in COS-7 cells from cloned cDNA. Cell structure and function 10 2111227
2023 Orobol, 3'-hydroxy-genistein, suppresses the development and regrowth of cutaneous SCC. Biochemical pharmacology 9 36657604
2022 Effects of Sensitized Sorafenib with a Paeoniflorin and Geniposide Mixture on Liver Cancer via the NF-κB-HIF-2α-SerpinB3 Pathway. Evidence-based complementary and alternative medicine : eCAM 9 36285158

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